Radiotherapy (RT) is an integral component in the management of early stage breast cancer following breast conservation and following mastectomy in high-risk patients. Previous reports have clearly documented, however, the potential for cardiac and pulmonary toxicity secondary to radiation injury, particularly in patients treated comprehensively to the regional nodes. Intensity modulated radiotherapy (IMRT) is a new treatment delivery technique that uses a variable intensity pattern determined with the aid of a computerized optimization algorithm. Preliminary results with IMRT in treatment of the breast only are promising with respect to improved target coverage and sparing of normal tissue. No studies to date, however, have prospectively compared the use of IMRT with the best standard three-dimensional (3-D) planning technique, with respect to cardiac and pulmonary exposure, in patients comprehensively treated to the breast/chest wall and regional nodes. Therefore, the long-term objective of the proposed research plan is to study comprehensive RT delivered using IMRT versus the best 3-D standard treatment technique (Partially Wide Tangential Fields (PWTF)). Quantitative indicators of potential cardiac and lung toxicity will be compared to determine the improvements that may be achieved with the new approach. Specific Aims: (1) Determine a static IMRT plan that significantly spares the heart and lung compared to the best static standard 3-D plan PWTF; (2) Evaluate the effect of delivery-related issues, such as respiratory motion and setup uncertainty, on static PWTF and IMRT plans from Aim 1, and produce plans that compensate for motion. Determine the optimal motion corrected plan between delivery-optimized PWTF and delivery-optimized IMRT. (3) Compare the best delivery-optimized technique from Aim 2 with the best standard 3-D technique, PWTF, in a prospective trial. With the pilot data generated through this proposal, a randomized trial will ultimately be performed comparing these two treatment delivery techniques. Study Design: (1) Establish cost functions that drive the optimization to develop the IMRT plan using heart, lung, opposite breast, and spinal cord constraints while maximizing target coverage to the breast/chest wall and nodes. Optimize the best IMRT plan for 20 static cases and compare the static IMRT plan with PWTF using heart and lung metrics. (2) Measure the distribution of setup errors and motion of target volumes in a cohort of 20 patients. Determine the effect of motion on static IMRT and PWTF dose distributions, and then correct/adjust for motion to determine the best delivery-optimized plan. (3) Study 60 patients treated with either the best delivery-optimized motion corrected plan from Aim 2 or PWTF and compare plans using heart and lung metrics.